title: Alendronate and atrial fibrillation: a meta-analysis of randomized placebo-controlled clinical trials.
abstract: In this meta-analysis of all Merck-conducted, placebo-controlled clinical trials of alendronate, the occurrence of AF was uncommon, with most studies reporting two or fewer events. Across all studies, no clear association between overall bisphosphonate exposure and the rate of serious or non-serious AF was observed.
  
  
  BACKGROUND
  To explore the incidence of atrial fibrillation (AF) and other cardiovascular endpoints in clinical trials of alendronate.
  
  
  METHODS
  All double-blind, placebo-controlled studies of alendronate 5, 10, or 20 mg daily, 35 mg once-weekly, 35 mg twice-weekly, and 70 mg once-weekly of at least 3 months duration conducted by Merck were included in this meta-analysis. The primary method of analysis was exact Poisson regression. Estimated relative risk (RR) of alendronate versus placebo and the associated 95% confidence interval was derived from a model that included number of episodes with factors for treatment group and study and an offset parameter for number of person-years on study.
  
  
  RESULTS
  Of 41 studies considered, 32 met all criteria for inclusion in the analysis (participants-9,518 alendronate, 7,773 placebo). Estimated RR for all AF events was 1.16 (95% CI = 0.87, 1.55; p = 0.33). Most trials had two or fewer AF events. The RR of AF classified as a serious adverse event was 1.25 (95% CI = 0.82, 1.93; p = 0.33), but became 0.97 (95% CI = 0.51, 1.85) when the clinical fracture cohort of the Fracture Intervention Trial was excluded, indicating that results were driven by events in that study. Estimated RRs for other cardiovascular endpoints were less than 1.
  
  
  CONCLUSIONS
  The incidence of atrial fibrillation was low in Merck clinical trials of alendronate and was not significantly increased in any single trial nor in the meta-analysis. Based on this analysis, alendronate use does not appear to be associated with an increased risk of atrial fibrillation.
authors.affiliation: University of California, San Diego, La Jolla, CA, USA. ebarrettconnor@ucsd.edu
authors.forename: E
authors.initials: E
authors.lastname: Barrett-Connor
authors.forename: A S
authors.initials: AS
authors.lastname: Swern
authors.forename: C M
authors.initials: CM
authors.lastname: Hustad
authors.forename: H G
authors.initials: HG
authors.lastname: Bone
authors.forename: U A
authors.initials: UA
authors.lastname: Liberman
authors.forename: S
authors.initials: S
authors.lastname: Papapoulos
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: A
authors.initials: A
authors.lastname: de Papp
authors.forename: A C
authors.initials: AC
authors.lastname: Santora
mesh_terms: D019386:Alendronate / Q000008:administration & dosage / Q000009:adverse effects*; D001281:Atrial Fibrillation / Q000139:chemically induced* / Q000453:epidemiology; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015994:Incidence; D010024:Osteoporosis / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic
chemical_list: D050071:Bone Density Conservation Agents; D019386:Alendronate